High-risk Papillary Thyroid Cancer Patients Research Articles

Nomogram for predicting skip metastasis in cN0 papillary thyroid cancer patients at increased risk of lymph node metastasis.

Skip lymph node metastasis (SLNM) refers to lateral lymph node metastasis (LLNM) without involving central lymph node (CLN). Some microscopic nodal positivity may be difficult to detect before surgery due to atypical imaging characteristics. These patients are misdiagnosed as having clinically node-negative (cN0) papillary thyroid cancer (PTC) even after central lymph node dissection, leading to a high risk of developing LNM after surgery. Current prediction models have limited clinical utility, as they are only applicable to predict SLNM from clinically node-positive (cN+) PTC, not cN0 PTC, and this has little impact on treatment strategies. This study aimed to establish a nomogram for preoperatively assessing the likelihood of SLNM in cN0 PTC patients with increased risk of LNM, thus optimizing their therapeutic options. The records of 780 PTC patients undergoing thyroidectomy along with bilateral central lymph node dissection were retrospectively reviewed. The cN0 patients with postoperative LLNM (occult SLNM) and cN+ patients without central lymph node metastasis (CLNM) (typical SLNM) were included in the SLNM group (n = 82). The CLNM-negative cN0 patients without postoperative LLNM were assigned to the non-SLNM group (n = 698). The independent correlates of SLNM constituted the nomogram for determining the likelihood of SLNM in high-risk cN0 PTC patients. The independent correlates of SLNM were age (hazard ratio (HR) = 1.016), tumor location (HR = 1.801), tumor size (HR = 1.528), and capsular invasion (HR = 2.941). They served as components in the development of the nomogram. This model was verified to present acceptable discrimination. It showed good calibration and a decent net benefit when the predicted probability was <60%. We developed a nomogram incorporating preoperative clinical data to predict the probability of SLNM development in high-risk cN0 PTC patients, which contributed to their optimized treatment options.

Analysis of Delayed Surgery and Clinical Outcomes in Intermediate- and High-risk Papillary Thyroid Cancer.

The optimal timing to performing thyroid surgery following a diagnosis of papillary thyroid cancer (PTC) has yet to be fully defined. We aimed to examine if a delayed surgery may worsen the clinical outcome of PTC patients with intermediate- to high-risk of recurrence. All consecutive PTC patients with intermediate- to high-risk of recurrence who underwent total thyroidectomy and radioactive iodine (RAI) ablation at 3 tertiary hospitals in southwest China were retrospectively included. Excellent response at 1-year follow-up after initial therapy was defined as no clinical, imaging, or biochemical evidence of PTC. Association of the timing of surgery and excellent response rates. The study included 871 patients. The median time interval between PTC diagnosis and surgery was 2 months (range, 1-87 months). Patients were divided according to the timing of surgery, < 6 months (group A, 624/871 [71.6%]), ≥ 6 to 11 months (group B, 123/871 [14.1%]), or ≥ 12 months (group C, 124/871 [14.2%]). One year after initial therapy, 64.7%, 71.5%, and 66.1% of patients in groups A, B, and C, respectively, achieved excellent response (P = 0.27). The lack of impact of surgery timing was observed across intermediate- to high-risk classifications and all T stage categories. These findings did not change when we separately analyzed the groups according to RAI dose (intermediate-dose group: ≤ 3.7 GBq [n = 654], and high-activity group: 5.5 GBq [n = 217]) further subdivided according to the timing of surgery. Timing of surgery does not seem to affect short-term disease outcomes in intermediate- to high-risk PTC patients. Further research is necessary to assess the impact of delayed surgery on long-term prognosis.

Association Between Preoperative US, Elastography Features and Prognostic Factors of Papillary Thyroid Cancer With BRAFV600E Mutation.

Purpose: To investigate the value of US and elastography for predicting prognostic factors of papillary thyroid cancer (PTC) in the positive BRAFV600E Mutation group.Materials and Methods: A total of 116 BRAFV600E Mutation patients with PTCs were enrolled in this prospective study, who were preoperatively evaluated by US, US elasticity imaging (EI), and Virtual Touch tissue imaging (VTI) and Virtual Touch tissue quantification (VTQ) of acoustic radiation force impulse (ARFI) imaging. Multivariate logistic regression analysis was performed to assess 23 independent variables for predicting prognostic factors. Diagnostic performance was evaluated with receiver operating characteristic (ROC) curve analysis.Results: Forty-two (36.2%) of 116 PTC patients with BRAFV600E Mutation had central lymph node metastasis (LNM). Nine (7.8%) and fifty-six (48.3%) had lateral LNM and extra-thyroidal extension (ETE), respectively. In multivariate logistic regression analyses, rich internal flow [odds ratio [OR]: 6.66] was the best predictor for central LNM, followed by male sex (OR: 4.22), halo sign absence (OR: 2.78) (all P < 0.05). VTQ ratio (OR: 1.57) was the only predictor for lateral LNM (P = 0.02). Rich internal flow (OR: 6.33) was the strongest predictor for ETE, followed by male sex (OR: 3.29), halo sign absence (OR: 2.90), and VTQ ratio (OR: 1.63) (all P < 0.05).Conclusion: VTQ ratio on ARFI imaging, rich internal flow and halo sign absence on US are the predicting prognostic factors in PTC patients with BRAFV600E Mutation. The specificities were significantly increased by combining ARFI imaging and US features, which has a potential to avoid unnecessary therapeutic neck dissection in the high-risk PTC patients.

Analysis of activity uptake, effective half-life and time-integrated activity for low- and high-risk papillary thyroid cancer patients treated with 1.11 GBq and 3.7 GBq of 131I-NaI respectively

PurposeTo analyse the activity uptakes, effective half-lives and time-integrated activities, of relevance for remnant dosimetry, for patients treated for papillary thyroid cancer (PTC) with a different amount of activity of 131I-NaI. MethodsFifty patients were included. Of those, 18 patients had low-risk PTC and were treated with 1.11 GBq of 131I-NaI (Group 1), and 32 patients had high-risk PTC and were treated with 3.7 GBq (Group 2). Radioiodine was administered after total thyroidectomy and rhTSH stimulation. Two SPECT/CT scans were performed for each patient to determine the remnant activities and effective half-lives. ResultsSignificantly higher values (p < 0.05) were obtained for Group 1 for the remnant activity at 7 d (medians 1.4 MBq vs 0.27 MBq), the remnant activity per administered activity at 2 d (0.35% vs 0.09%) and at 7 d (0.13% vs 0.007%), and the effective half-life (93 h vs 40 h). Likewise, the time-integrated activity coefficient was significantly higher for Group 1. The time-integrated activity did not differ significantly between the two groups (p > 0.05). ConclusionsWe found a significant difference in the remnant activity per administered activity, the rate of washout from thyroid remnants, and the time-integrated activity coefficient between low-risk PTC patients treated with 1.11 GBq and high-risk PTC patients treated with 3.7 GBq. On the contrary, there was no such difference in the time-integrated activity. If remnant masses were also not statistically different (reasonable assumption for this monocentric study) no difference in time-integrated activity would imply no difference in remnant absorbed dose, of relevance for treatment efficacy and the risks of stochastic effects.

Disparity in the use of adjuvant radioactive iodine ablation among high-risk papillary thyroid cancer patients

BackgroundWe sought to identify treatment disparities existing prior to publication of the 2015 American Thyroid Association Management Guidelines in order to identify patients with papillary thyroid cancer (PTC) at risk for receiving inadequate treatment. MethodsPatients diagnosed with PTC from 2011 to 2013 were identified using Surveillance, Epidemiology and End Results database. High-risk disease was defined as T4, N1, or M1. Chi-square tests compared characteristics of patients with and without high-risk disease and characteristics of high-risk patients who did and did not receive radioactive iodine ablation (RAI). Likelihoods of having high-risk disease, of receiving RAI, and of cause-specific death were calculated using regression analyses. ResultsSample included 32,229 individuals; 7894 (24.5%) had high-risk disease. Mean age was 50.0 years, 24,815 (77.0%) were female, and 21,318 (66.2%) were white. Odds of high-risk disease were greater among males (OR:2.04; 95% CI:1.92–2.16), Hispanics (OR:1.67; 95% CI:1.56–1.79) and Asians (OR:1.49; 95% CI:1.37–1.62), and uninsured (OR:1.24; 95% CI:1.07–1.43), and lower among patients ages 45–64 (OR:0.57; 95% CI:0.53–0.60), and ≥65 years (OR:0.54; 95% CI:0.50–0.59), and Blacks (OR:0.46; 95% CI:0.40–0.53). Most (69.3%) high-risk patients received RAI. Odds of receiving RAI were lower among patients age ≥65 years (OR:0.67; 95% CI:0.58–0.77), uninsured (OR:0.52; 95% CI:0.41–0.67), or with Medicaid (OR:0.58; 95% CI:0.50–0.69). RAI use reduced the risk of cause-specific mortality (HR:0.29; 95% CI:0.18–0.47). ConclusionKnowledge of these treatment disparities will allow recognition of groups at risk for high-risk disease and receiving inadequate treatment.

Is TSH suppression still necessary in intermediate- and high-risk papillary thyroid cancer patients with pre-ablation stimulated thyroglobulin

Since papillary thyroid cancer (PTC) patients with pre-ablation stimulated thyroglobulin (s-Tg) < 1 ng/mL generally have a favorable prognosis, is TSH suppression still necessary in intermediate- and high-risk PTC patients with pre-ablation s-Tg < 1 ng/mL after initial therapy? The aim of this study was to assess the rate of disease recurrence in intermediate- and high-risk PTC patients with pre-ablation s-Tg < 1 ng/mL according to TSH levels measured 1 year after initial therapy. A retrospective series of intermediate- and high-risk PTC patients with pre-ablation s-Tg < 1 ng/mL was analyzed. Disease status was defined as the presence or absence of structural disease during late follow-up. Patients were grouped according to TSH level at 1 year: group 1, TSH < 0.1 mIU/L; group 2, TSH 0.1‒0.5 mIU/L; group 3, 0.5‒2 mIU/L; group 4, >2 mIU/L. This study included 166 patients (78.3% females, median age 44 years) of whom the risk of recurrence was intermediate in 97 (58.4%) and high in 69 (41.6%). The response to initial therapy at 1 year was excellent in 163 patients (98.2%) and indeterminate in 3 (1.8%). Group 1 consisted of 63 patients (38%), group 2 of 47 (28%), group 3 of 28 (17%), and group 4 of 28 (17%). During a median follow-up duration of 5.8 years, disease recurrence was observed in only 4 patients (2.4%). The rate of disease recurrence was not significantly different between the TSH groups. TSH suppression before the first response to treatment assessment does not seem to influence the rate of disease recurrence after initial therapy in intermediate- and high-risk PTC patients with pre-ablation s-Tg < 1 ng/mL.

Prognosis of High-Risk Papillary Thyroid Cancer Patients with Pre-Ablation Stimulated TG

The prevalence of undetectable pre-ablation stimulated thyroglobulin (s-Tg) and its clinical implications in high-risk papillary thyroid cancer (PTC) patients remain poorly described. We investigated the rate of tumor recurrence in PTC patients initially classified as high risk but with pre-ablation s-Tg <1 ng/mL and negative anti-Tg antibody (TgAb). In order to have a follow-up period of at least 5 years for each patient, PTC patients consecutively seen at our department from May 2008 to June 2013 with the following characteristics were selected: (i) classified as American Thyroid Association high risk on the basis of tumor histopathologic features; (ii) submitted to adjuvant 131I therapy after total thyroidectomy; (iii) a postoperative pre-ablation s-Tg <1 ng/mL and negative TgAb. Among 767 high-risk PTC patients submitted to adjuvant 131I therapy, 69 patients met the inclusion criteria. Sixty-seven patients (97.1%) were diagnosed as classical PTC, and the remaining 2 patients (2.9%) were diagnosed as follicular variant PTC. When evaluated 9 to 12 months after 131I therapy, 67 patients (97.1%) were classified as excellent response. Two (2.9%) patients had an s-Tg >1 ng/mL (<3 ng/mL) in the absence of apparent disease, as detected by imaging methods (indeterminate response). During a median follow-up duration of 5.6 years, recurrence was observed in only 2 (2.9%) patients. The 67 (97.1%) patients without tumor recurrence were not submitted to any additional therapy, and all had a suppressed Tg <1 ng/mL in the last assessment. High-risk PTC patients with pre-ablation s-Tg <1 ng/mL and negative TgAb had a favorable prognosis. CT = computed tomography; L-T4 = levothyroxine; PTC = papillary thyroid cancer; SPECT/CT = single photon emission computed tomography/computed tomography; s-Tg = stimulated thyroglobulin; T4 = thyroxine; TgAb = anti-thyroglobulin antibody; US = ultrasound.

Prediction of Ipsilateral and Contralateral Cervical Lymph Node Metastasis in Unilateral Papillary Thyroid Carcinoma

Background: Surgical therapy is the cornerstone of treatment in patients with papillary thyroid cancer (PTC). Surgical therapy in PTC includes hemithyroidectomy or total thyroidectomy (TT) and, in cases of lymph node metastases, cervical lymph node dissection (CLND). The inclusion of prophylactic central compartment neck dissection (pCCND) as a new approach in the management of patients with PTC with clinically negative cervical lymph nodes raised controversies among the endocrine surgeons and predictive factors for central lymph node (CLN) metastasis in unilateral PTC cases not well defined. Objectives: To investigate the risk factors associated with CLNM in clinical lateral cervical lymph node?negative (cN0) and analyze the rate of ipsilateral and contralateral CLN metastasis in unilateral PTC casesin Al Azhar University Hospitals in the period from May 2016 tillJune 2018. Patients and Methods: A prospective case-control descriptive study was performed to investigate the research questions during the period from the 1st of May 2016 till the end of June 2018 in Al-Azhar University Hospitals. A total of 40 selected patients suffering from papillary thyroid with clinically negative cervical lymph nodes who have received total thyroidectomy with bilateral CLND. The clinicopathological features of PTC patients with respect to sex, age, observation, tumor diameter, multifocality, extrathyroidal invasion, lymphovascular invasion and capsular invasion. The risk factors of CLNM were analyzed by Chi-squared test and multivariate logistic regression model. Results: Ipsilateral CLN metastasis were present in 47.5% (19/40).Results analysis showed that males patients with tumor size (>1 cm) (P=0.027; OR, 2.153), age <45 years old (P=0.017; OR, 2.009) and capsular invasion (P= 0.018; OR= 0.730) were the predictors of ipsilateral CLN metastasis.Contralateral CLN metastasis were present in 17.5% (7/40) and prelaryngeal lymph node (LN) metastasis (P=0.008; OR, 13.333) and ipsilateral CLN metastasis (P=0.051; OR, 9.231), pretracheal lymph nodes (P=0.051; OR, 9.231), lymphovascular invasion (P=0.043; OR, 5.113) and ETE (P=0.05; OR, 4.901) independently predicted contralateral CLN metastasis. Conclusion: For the high-risk PTC patients with CLNM, prophylactic CLND may be beneficial. Nevertheless, the present data was a single center prospective analysis, and the long-term prognostic factors including recurrence rate and mortality rate were lacking. Therefore, the results of this research may only serve as a tool in predicting CLNM.

30mCi radioactive iodine achieving comparative excellent response in intermediate/high-risk nonmetastatic papillary thyroid cancer: a propensity score matching study.

To determine the efficacy of low-dose radioactive iodine (RAI) therapy (30 mCi, 1110 MBq) in Chinese patients with intermediate- to high-risk papillary thyroid cancer (PTC) without distant metastasis. This large retrospective study included Chinese patients with PTC that tested negative for thyroglobulin antibodies. Patients were categorized into low-dose (30 mCi, 1110 MBq) and high-dose (>100 mCi, 3700 MBq) RAI groups. Ablation rate and long-term response were compared between groups using propensity score matching (PSM) to minimize bias and confounding. In total, we included 446 patients. No significant difference in ablation success rate was found between groups (P = 0.305) before or after PSM (N = 162; P = 0.200). Excellent response (ER) rate was not significant between groups before (P = 0.917) or after PSM (P = 0.798). Efficacy of low-dose RAI was similar to that of high-dose RAI in N0- (P = 1.000), N1a- (P = 0.981), and N1b-stage (P = 0.903) patients. Low- and high-dose RAI groups achieved similar ER rates in pre-ablative stimulated thyroglobulin level (≤1 ng/mL, P = 1.000; 1 < ps-Tg ≤ 5 ng/mL, P = 0.444; 5 < ps-Tg ≤ 10 ng/mL, P = 0.665; >10 ng/mL, P = 1.000) and BRAFV600E-positive (P = 0.324) subgroups. Efficacy of low-dose RAI therapy was similar to that of high-dose for ablation and achieving ER in Chinese nonmetastatic intermediate- to high-risk PTC patients. High-dose RAI could not rectify ablation failure or non-ER rates in PTC patients with BRAFV600E, lymph node metastases, or unfavorable thyroglobulin levels.

Cost-effectiveness analysis of papillary thyroid cancer surveillance.

The recent overdiagnosis of subclinical, low-risk papillary thyroid cancer (PTC) coincides with a growing national interest in cost-effective health care practices. The aim of this study was to measure the relative cost-effectiveness of disease surveillance of low-risk PTC patients versus intermediate- and high-risk patients in accordance with American Thyroid Association risk categories. Two thousand nine hundred thirty-two patients who underwent thyroidectomy for differentiated thyroid cancer between 2000 and 2010 were identified from the institutional database; 1845 patients were excluded because they had non-PTC cancer, underwent less than total thyroidectomy, had a secondary cancer, or had <36 months of follow-up. In total, 1087 were included for analysis. The numbers of postoperative blood tests, imaging scans and biopsies, clinician office visits, and recurrence events were recorded for the first 36 months of follow-up. Costs of surveillance were determined with the Physician Fee Schedule and Clinical Lab Fee Schedule of the Centers for Medicare and Medicaid Services. The median age was 44 years (range, 7-83 years). In the first 36 months after thyroidectomy, there were 3, 44, and 22 recurrences (0.8%, 7.8%, and 13.4%) in the low-, intermediate-, and high-risk categories, respectively. The cost of surveillance for each recurrence detected was US $147,819, US $22,434, and US $20,680, respectively. The cost to detect a recurrence in a low-risk patient is more than 6 and 7 times greater than the cost for intermediate- and high-risk PTC patients. It is difficult to justify this allocation of resources to the surveillance of low-risk patients. Surveillance strategies for the low-risk group should, therefore, be restructured.

Detection of Residual Lymph Node Metastases in High-Risk Papillary Thyroid Cancer Patients Receiving Adjuvant I-131 Therapy

The aims of this retrospective study were to evaluate the incidence of residual lymph node (LN) metastases in high-risk papillary thyroid cancer (PTC) patients receiving adjuvant I-131 therapy, especially in those without I-131 accumulation, and to evaluate the clinical usefulness of F-18 FDG PET/CT to detect those lesions. The 37 PTC patients receiving adjuvant I-131 therapy were retrospectively evaluated. We examined the incidence of residual LN metastasis and compared the accumulation of F-18 FDG and I-131 in those lesions, and compared the serum thyroglobulin (Tg) levels between patients with and without residual LN metastases. A total of 33 lesions were diagnosed as residual LN metastases in 9 patients. FDG accumulated in all of the lesions, but 19 lesions (57.6%) of them had no I-131 accumulation. The SUVmax was significantly higher in lesions without I-131 accumulation than in lesions with I-131 accumulation (6.6 +/- 2.8 vs. 4.2 +/- 1.8; P = 0.007). The serum Tg levels were significantly higher in patients with residual LN metastases than in patients without it (709.9 +/- 1470.8 vs. 25.6 +/- 37.1 ng/mL; P = 0.005). The incidence of residual LN metastasis was significantly higher in patients with a detectable serum Tg level than in patients without it (35.0% vs. 0%, P = 0.03). These results indicate that the residual LN metastasis was relatively common in high-risk PTC patients receiving adjuvant I-131 therapy whose serum Tg levels remained detectable, and those lesions often had no I-131 accumulation. FDG-PET/CT would be recommended for PTC patients with detectable serum Tg levels to detect residual LN metastases.